Ipragliflozin Additively Ameliorates Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Controlled with Metformin and Pioglitazone: A 24-Week Randomized Controlled Trial

Han, Eugene; Lee, Yongho; Lee, Byung Wan; Kang, Eun Seok; Soo, Bong

doi:10.3390/jcm9010259

Cited by 54 publications

(76 citation statements)

References 35 publications

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“…56,57 All studies were limited by small samples; studies included adult patient populations with T2DM and ranged from 20 to 56 weeks in duration. 52-58…”

Section: Resultsmentioning

confidence: 99%

“…Han et al 53 compared the additive effect of ipragliflozin 50 mg in T2DM patients with NAFLD already on pioglitazone and metformin therapy to pioglitazone and metformin alone. Significant reductions in fatty liver index and NAFLD liver fat score were observed.…”

Section: Resultsmentioning

confidence: 99%

“…However, no significant reduction in CAP was seen after the addition of SGLT2 inhibitors in addition to pioglitazone and metformin. 53…”

Section: Resultsmentioning

confidence: 99%

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A Systematic Review of Newer Antidiabetic Agents in the Treatment of Nonalcoholic Fatty Liver Disease

2020

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Objective: To evaluate glucagon-like peptide 1 receptor agonists (GLP-1 RAs), dipeptidyl-peptidase IV (DPP-4) inhibitors, and sodium-glucose cotransporter 2 (SGLT) inhibitors to treat nondiabetic and type 2 diabetes mellitus (T2DM) nonalcoholic fatty liver disease (NAFLD) as it relates to improvement in hepatosteatosis (HS) or steatohepatitis (SH). Data Sources: MEDLINE and CINAHL were searched from inception through May 1, 2020. Search terms included nonalcoholic steatohepatitis, nonalcoholic fatty liver disease, fatty liver, dipeptidyl-peptidase IV inhibitors, glucagon-like peptide-1 receptor agonists, and sodium-glucose transporter 2 inhibitors. Study Selection and Data Extraction: Full-text observational and randomized controlled studies in English were included. Patients diagnosed with NAFLD, treated with GLP-1 RAs, DPP-4 inhibitors, and SGLT2 inhibitors, with measures to evaluate HS or SH were evaluated. Data Synthesis: Eight GLP-1 RA trials were reviewed; 7 GLP-1 RA trials showed improvement in HS. Two studies demonstrated improvement in liver histology in patients with SH. Seven SGLT2 inhibitor studies were reviewed; 6 studies demonstrated improvements in NAFLD. Five studies showed improvements in HS, whereas 1 displayed improvement in liver histology in NASH. Six studies that included DPP-4 inhibitors were evaluated, and only 2 demonstrated improvement in NASH. Relevance to Patient Care and Clinical Practice: Based on evidence reviewed, GLP-1 RAs and SGLT2 inhibitors decreased HS and SH in NAFLD patients, whereas DPP-4 inhibitor therapy was not effective for patients with HS. Conclusions: Based on study data utilizing imaging studies and biopsy results, GLP-1 RAs or SGLT2 inhibitors can benefit NAFLD T2DM patients. Clinical trials with larger patient populations may augment these results.

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“…56,57 All studies were limited by small samples; studies included adult patient populations with T2DM and ranged from 20 to 56 weeks in duration. 52-58…”

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

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A Systematic Review of Newer Antidiabetic Agents in the Treatment of Nonalcoholic Fatty Liver Disease

2020

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“…93 Furthermore, ipragliflozin (50 mg daily) treatment for 24 weeks significantly ameliorated liver steatosis and reduced excessive fat in 44 euglycemic patients with T2DM and NAFLD who were taking metformin and pioglitazone at baseline. 94…”

Section: Ipragliflozinmentioning

confidence: 99%

Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease

Kim

Lee

2020

Clin Mol Hepatol

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Nonalcoholic fatty liver disease (NAFLD) is the most common liver disorder and is associated with various metabolic diseases, including type 2 diabetes mellitus. There are no approved drugs for NAFLD, and the only approved treatment option is weight reduction. As insulin resistance plays an important role in the development of NAFLD, many anti-diabetic drugs have been evaluated for the treatment of NAFLD. Improvement of liver enzymes has been demonstrated by many anti-diabetic drugs, but histological assessment still remains insufficient. Pioglitazone could become the first-line therapy for T2DM patients with NAFLD, based on evidence of histological improvement in patients with biopsy-proven nonalcoholic steatohepatitis (NASH). Liraglutide, another promising alternative, is not yet recommended in patients with NAFLD/NASH due to limited evidence. Therefore, well-designed randomized controlled trials should be performed in the near future to demonstrate if and how anti-diabetic drugs can play a role in the treatment of NAFLD.

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“…110,111 A recent Korean study observed that ipragliflozin use was associated with improved hepatic and visceral fat content and liver enzymes. 112 These trials are presented in Table 2.…”

Section: Other Sglt2 Inhibitorsmentioning

confidence: 99%

A look to the future in non‐alcoholic fatty liver disease: Are glucagon‐like peptide‐1 analogues or sodium‐glucose co‐transporter‐2 inhibitors the answer?

Vincent

Williams

Evans

2020

Diabetes Obesity Metabolism

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The increasing prevalence of diabetes and non-alcoholic fatty liver disease (NAFLD) is a growing public health concern associated with significant morbidity, mortality and economic cost, particularly in those who progress to cirrhosis. Medical treatment is frequently limited, with no specific licensed treatments currently available for people with NAFLD. Its association with diabetes raises the possibility of shared mechanisms of disease progression and treatment. With the ever-growing interest in the non-glycaemic effects of diabetes medications, studies and clinical trials have investigated hepatic outcomes associated with the use of drug classes used for people with type 2 diabetes (T2D), such as glucagon-like peptide-1 (GLP-1) analogues or sodium-glucose co-transporter-2 (SGLT2) inhibitors. Studies exploring the use of GLP-1 analogues or SGLT2 inhibitors in people with NAFLD have observed improved measures of hepatic inflammation, liver enzymes and radiological features over short periods. However, these studies tend to have variable study populations and inconsistent reported outcomes, limiting comparison between drugs and drug classes. As these drugs appear to improve biomarkers of NAFLD, clinicians should consider their use in patients with NAFLD and T2D. However, further evidence with greater participant numbers and longer trial durations is required to support specific licensing for people with NAFLD. Larger trials would allow reporting of major adverse hepatic events, akin to cardiovascular and renal outcome trials, to be determined. This would provide a more meaningful evaluation of the impact of these drugs in NAFLD. Nevertheless, these drugs represent a future potential therapeutic avenue in this difficult-totreat population and may beget significant health and economic impacts.

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Ipragliflozin Additively Ameliorates Non-Alcoholic Fatty Liver Disease in Patients with Type 2 Diabetes Controlled with Metformin and Pioglitazone: A 24-Week Randomized Controlled Trial

Cited by 54 publications

References 35 publications

A Systematic Review of Newer Antidiabetic Agents in the Treatment of Nonalcoholic Fatty Liver Disease

A Systematic Review of Newer Antidiabetic Agents in the Treatment of Nonalcoholic Fatty Liver Disease

Beneficial effect of anti-diabetic drugs for nonalcoholic fatty liver disease

A look to the future in non‐alcoholic fatty liver disease: Are glucagon‐like peptide‐1 analogues or sodium‐glucose co‐transporter‐2 inhibitors the answer?

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